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IEEE TRANSACTIONS ON NUCLEAR SCIENCE, VOL. 50, NO. 1, FEBRUARY 2003

Addressing the Third Gamma Problem in PET

M. J. Schueller, T. L. Mulnix, B. T. Christian, M. Jensen, S. Holm, T. R. Oakes, A. D. Roberts, D. W. Dick, C. C. Martin, and R. J. Nickles

AbstractPET brings the promise of quantitative imaging of the in-vivo distribution of any positron emitting nuclide, a list with hundreds of candidates. All but a few of these, the pure positron emitters, have isotropic coincident gamma rays that give rise to misrepresented events in the sinogram and in the resulting reconstructed image. Of particular interest are 10 C, 14 O, 38 K, 52 Mn, 60 Cu, 61 Cu, 94 Tc, and 124 I, each having high-energy gammas that are Compton-scattered down into the 511 keV window. The problems arising from the third gamma, and its accommodation by standard scatter correction algorithms, were studied empirically, employing three scanner models (CTI 933/04, CTI HR+ and GE Advance), imaging three phantoms (line source, NEMA scatter and contrast/detail), with 18 F or 38 K and 72 As mimicking 14 O and 10 C, respectively, in 2-D and 3-D modes. Five findings emerge directly from the image analysis. The third gamma: 1)does, obviously, tax the single event rate of the PET scanners, particularly in the absence of septa, from activity outside of the axial field of view; 2) does, therefore, tax the random rate, which is second order in singles, although the gamma is a prompt coincidence partner; 3) does enter the sinogram as an additional flat background, like randoms, but unlike scatter; 4) is not seriously misrepresented by the scatter algorithm which fits the correction to the wings of the sinogram; and 5) does introduce additional statistical noise from the subsequent subtraction, but does not seriously compromise the detectability of lesions as seen in the contrast/detail phantom. As a safeguard against the loss of accuracy in image quantitation, fiducial sources of known activity are included in the field of view alongside of the subject. With this precaution, a much wider selection of imaging agents can enjoy the advantages of positron emission tomography. Index TermsPositron emission tomography (PET), third gamma interference.

TABLE I AN ABBREVIATED LIST OF PET RADIONUCLIDES WITH COINCIDENT GAMMA DE-EXCITATION

I. INTRODUCTION N its four decades of history, positron emission tomography (PET) has focused principally on the imaging of tracers labeled with C, N, O and F. This is due to several factors. 1) The biochemical importance of their compounds.

Manuscript received April 19, 2001; revised September 26, 2002. M. J. Schueller is with the Brookhaven National Lab, Upton, NY 11973 USA (e-mail: mschueller@bnl.gov). T. L. Mulnix is with the CTI Inc., Knoxville, TN 37932 USA (e-mail: tim.mulnix@cti-pet.com). B. T. Christian is with the Kettering Medical Center, Kettering, OH 45429 USA (e-mail: brad.christian@kmcnetwork.org). M. Jensen and S. Holm are with the Rigshospitalet, Copenhagen 2100 DK, Denmark (e-mail: mikaelj@pet.rh.dk; sholm@pet.rh.dk). T. R. Oakes, A. D. Roberts, D. W. Dick, and R. J. Nickles are with the University of Wisconsin-Madison, Madison, WI 53706 USA (e-mail: oakes@psyphw.psych.wisc.edu; arobert5@facstaff.wisc.edu; dwdick@petrus. medphysics.wisc.edu; nickles@petrus.medphysics.wisc.edu). C. C. Martin was with the University of Wisconsin-Madison, Madison, WI 53706 USA. He is now with SciBiz, Madison, WI 53705 USA (e-mail: cmartin@scibizbridge.com). Digital Object Identifier 10.1109/TNS.2002.807868

2) Their ready accessibility from small cyclotrons. 3) Their favorable decay characteristics, namely a decay half-life well matched to biological rate constants. 4) A clean positron decay, unburdened with additional de-excitation gamma rays. More than 100 other positron emitters populate the proton rich side of the valley of beta stability, ranging from C to the rare earths, where electron capture finally overwhelms positron decay leads decay, favored by Coulomb effects. Generally, to excited states of the daughter, resulting in subsequent de-excitation on the order of nanoseconds. Table I presents a short list of positron emitters that have been studied at our host institutions for various biological applications, along with their half-lives, major signature gamma and production reaction. The extra gammas listed in Table I are problematic because they annihilaare in prompt coincidence with the two 511 keV tion photons and are spatially uncorrelated with their direction, as indicated in Fig. 1. Their most probable interaction in the PET scanner detector is a Compton scatter event, quite likely depositing energy within the 350850 keV window. The isotropy of the relative to the 511 keV photons results in a large phase space of acceptance by the scanner detector blocks to activity axially displaced out of the field of view of the scanner. The redeeming feature of this isotropy is that the events are evenly distributed across the entire sinogram and contribute only a low frequency background to the reconstructed image. Nonetheless, the magnitude of this additional background and the effect of the scatter correction algorithm in sweeping it under the rug must be addressed by an empirical investigation [1], [2] of each scanner, with each radionuclide, by imaging phantoms that challenge spatial resolution and quantitative recovery. This report describes a multi-center program toward that end.

0018-9499/03$17.00 2003 IEEE

SCHUELLER et al.: ADDRESSING THE THIRD GAMMA PROBLEM IN PET

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Fig. 1. Illustration of the third gamma problem. One of the coincidence gammas due to positron annihilation is not detected, but the third gamma, undergoing Compton scatter in the detector, gives rise an event misregistration.

Fig. 3. The 3-D slices of the contrast-detail phantom (top), the NEMA scatter phantom (center) and the line-source surrounded by a scattering medium (bottom). The background activity is provided by As, which has similar third-gamma properties as C.

Fig. 2. The contrast/detail phantom (left) with a close-up view (right) showing the variation in diameter of the tubes.

Fig. 4. NEC curves for O (pure  ) and K( + ) using the NEMA phantom in a GE Advance scanner in 2-D and 3-D modes. The NEC equation used was NEC = T=(1 +  +  ) [3]. The scatter fraction values used were 0. 1 for 2-D and 0.4 for 3-D. The graph shows an almost two-fold decrease in NEC for K in both 2-D and 3-D modes, which is attributed to the third gamma.

II. METHODS Three types of scanners were exercised: 1) UW Medical Physics Dept CTI 933/04, a 1986-vintage 7-slice, 2-D scanner; 2) two CTI HR+s at the factory in Knoxville, TN; 3) two GE Advancesone at the UW Keck Lab and the other at Rigshospital, Copenhagen. Three phantoms were built for this work: 1) contrast/detail phantom; 2) NEMA scatter phantom; 3) line source surrounded by a scattering medium. The contrast/detail phantom (Fig. 2) has 5 sets of tubes of increasing diameter (1/16", 1/8", 3/16", 1/4", 1/2") filled with 6 levels of activity (1, 0.8, 0.6, 0.4, 0.2, 0.1 Ci/ml). To insure a reasonable shelf life of this phantom, the positron emitter inside the tubes consists of Na in a solid matrix (polyethylene glycol, C). This 5 6 tube array was mounted in a tank of short-lived activity (e.g., F) to smoothly sequence from warm rods/hot background to warm rods/cool background. Two classes of positron emitters were imaged:

1) pure ( C, F); ( C, K, As). 2) Data was acquired in both 2-D and 3-D. Finally, reconstruction was performed using filtered back projection, although it has become clear that the isodetectablility loci in the contrast/detail images favor OSEM. III. RESULTS The images in Fig. 3 show 3-D slices with As (mimicking C), which must be compared to their 2-D counterparts, as must the F equivalents. Briefly 1) All scanners suffered from additional noise, scatter and sources, with an almost randoms when imaging two-fold decrease in NEC [3] for brain-sized fields as seen in Fig. 4. 2) The gross quantitation of absolute activity and contrast in the image is preserved, both in 2-D and 3-D. This should be verified by including fiducial sources of known activity in the field of view, making activity normalization straightforward.

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IEEE TRANSACTIONS ON NUCLEAR SCIENCE, VOL. 50, NO. 1, FEBRUARY 2003

Fig. 6. Paired [ C]-CO flow maps of a normal subject, with rest (left) and visual stimulation (right) clearly distinguished in a three-minute steady-state study.

the additional prompt coincidence events that have no valid position information associated with them, they are being cast uniformly across the reconstructed image. Thus, aside from the additional statistical noise, lesion detection is only slightly compromised as shown by an increased locus of isodetectability, shown in Fig. 5. IV. CONCLUSION Clearly, no benefit comes from the third gamma. It is detrimental to scanner loading, image quality and patient dose. Yet each of the candidates of Table I have compelling reasons to join a wider set of PET tracers, as suggested by the demonstration images in Fig. 6. The third gamma warrants careful treatment. It is not grounds for paralysis. REFERENCES
[1] M. J. Schueller, Investigating H O and CO as Cerebral Blood Flow Tracers With PET, Ph.D. dissertation, Medical Physics Dept., Univ. Wisconsin-Madison, 2001. [2] M. Lubberink, Quantitative Imaging With PET, Performance and ApIn and La, Ph.D., Uppsala Univ., plications of Br, Fe, 2001. [3] S. C. Strother, M. E. Casey, and E. J. Hoffman, Measuring PET scanner sensitivity: Relating count rates to image signal-to-noise ratios using noise equivalent counts, IEEE Trans. Nucl. Sci., vol. 37, pp. 783788, Apr. 1990.

Fig. 5. Contrast/detail results for hot rods against a warm background of F, a pure  emitter (top) and As, which emits a  as well as a third (bottom). Images are acquired for the given number of events in the sinogram (30K, 100K, . . ., 3M counts), reconstructed and read by several observers. For each bar diameter, the contrast level at which the bar becomes barely discernible is recorded, forming a locus of isodetectibility.

3) The scatter correction is slightly undercorrected in the sources, to be expected from algorithms case of unprepared for a new class of events (prompt coincidence, but isotropic) that are flooding the detectors. 4) The contrast/detail phantom re-assures us that although the scanner is quietly working very hard to process